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Frontiers in Endocrinology 2024
Topics: Oocytes; Aging
PubMed: 38298380
DOI: 10.3389/fendo.2024.1361115 -
Science Advances Nov 2023BMP15 is a conserved regulator of ovarian development and maintenance in vertebrates. In humans, premature ovarian insufficiency is caused by autoimmunity and genetic...
BMP15 is a conserved regulator of ovarian development and maintenance in vertebrates. In humans, premature ovarian insufficiency is caused by autoimmunity and genetic factors, including mutation of BMP15. The cellular mechanisms underlying ovarian failure caused by BMP15 mutation and immune contributions are not understood. Using zebrafish, we established a causal link between macrophage activation and ovarian failure, which, in zebrafish, causes sex reversal. We define a germline-soma signaling axis that activates macrophages and drives ovarian failure and female-to-male sex reversal. Germline loss of zebrafish Bmp15 impairs oogenesis and initiates this cascade. Single-cell RNA sequencing and genetic analyses implicate ovarian somatic cells that express conserved macrophage-activating ligands as mediators of ovarian failure and sex reversal. Genetic ablation of macrophages or elimination of Csf1Rb ligands, Il34 or Csf1a, delays or blocks premature oocyte loss and sex reversal. The axis identified here provides insight into the cells and pathways governing oocyte and ovary maintenance and potential therapeutic targets to preserve female fertility.
Topics: Humans; Animals; Male; Female; Zebrafish; Macrophage Activation; Oocytes; Primary Ovarian Insufficiency
PubMed: 37992158
DOI: 10.1126/sciadv.adg7488 -
International Journal of Gynaecology... Dec 2023Fertility preservation is a growing field in reproductive medicine that may raise ethical questions. Preservation of fertility must be discussed with the patient if...
Fertility preservation is a growing field in reproductive medicine that may raise ethical questions. Preservation of fertility must be discussed with the patient if gonadotoxic treatment is required, whether in the case of benign or malignant pathology, or in the management of transgender identity. As a result, surgery or chemotherapy that has fewer adverse impacts on fertility should be proposed if this does not alter the prognosis of the disease. If the risk of infertility persists, then fertility cryopreservation should be proposed for children and adults of reproductive age. Sperm, oocytes, and gonadal tissue can be cryopreserved for many years. FIGO wishes to emphasize the importance of fertility preservation in the medical and surgical management of patients, and the importance of a specialized, multidisciplinary approach.
Topics: Child; Adult; Humans; Male; Fertility Preservation; Semen; Cryopreservation; Oocytes; Infertility; Neoplasms
PubMed: 37807831
DOI: 10.1002/ijgo.15187 -
Cell Proliferation Dec 2023Normal ovarian development is necessary for the production of healthy oocytes. However, the characteristics of oocytes development at different stages and the regulatory...
Normal ovarian development is necessary for the production of healthy oocytes. However, the characteristics of oocytes development at different stages and the regulatory relationship between oocytes and somatic cells remain to be fully explained. Here, we combined scRNA-seq and spatial transcriptomic sequencing to profile the transcriptomic atlas of developing ovarian of the rat. We identified four components from developing granulosa cells including cumulus, primitive, mural, and luteal cells, and constructed their differential transcriptional regulatory networks. Several novel growth signals from oocytes to cumulus cells were identified, such as JAG1-NOTCH2 and FGF9-FGFR2. Moreover, we observed three cumulus sequential phases during follicle development determined by the key transcriptional factors in each cumulus phase (Bckaf1, Gata6, Cebpb, etc.), as well as the potential pinpointed roles of macrophages in luteal regression. Altogether, the single-cell spatial transcriptomic profile of the ovary provides not only a new research dimension for temporal and spatial analysis of ovary development, but also valuable data resources and a research basis for in-depth excavation of the mechanisms of mammalian ovary development.
Topics: Female; Rats; Animals; Ovary; Oocytes; Granulosa Cells; Oogenesis; Transcriptome; Mammals
PubMed: 37309718
DOI: 10.1111/cpr.13516 -
Nucleic Acids Research Dec 2023Translation is critical for development as transcription in the oocyte and early embryo is silenced. To illustrate the translational changes during meiosis and...
Translation is critical for development as transcription in the oocyte and early embryo is silenced. To illustrate the translational changes during meiosis and consecutive two mitoses of the oocyte and early embryo, we performed a genome-wide translatome analysis. Acquired data showed significant and uniform activation of key translational initiation and elongation axes specific to M-phases. Although global protein synthesis decreases in M-phases, translation initiation and elongation activity increases in a uniformly fluctuating manner, leading to qualitative changes in translation regulation via the mTOR1/4F/eEF2 axis. Overall, we have uncovered a highly dynamic and oscillatory pattern of translational reprogramming that contributes to the translational regulation of specific mRNAs with different modes of polysomal occupancy/translation that are important for oocyte and embryo developmental competence. Our results provide new insights into the regulation of gene expression during oocyte meiosis as well as the first two embryonic mitoses and show how temporal translation can be optimized. This study is the first step towards a comprehensive analysis of the molecular mechanisms that not only control translation during early development, but also regulate translation-related networks employed in the oocyte-to-embryo transition and embryonic genome activation.
Topics: Embryonic Development; Gene Expression Regulation, Developmental; Meiosis; Oocytes; Protein Biosynthesis; RNA, Messenger; Animals; Mice
PubMed: 37950888
DOI: 10.1093/nar/gkad996 -
Journal of Translational Medicine Oct 2023CRISPR/Cas9, a highly versatile genome-editing tool, has garnered significant attention in recent years. Despite the unique characteristics of oocytes and early embryos... (Review)
Review
CRISPR/Cas9, a highly versatile genome-editing tool, has garnered significant attention in recent years. Despite the unique characteristics of oocytes and early embryos compared to other cell types, this technology has been increasing used in mammalian reproduction. In this comprehensive review, we elucidate the fundamental principles of CRISPR/Cas9-related methodologies and explore their wide-ranging applications in deciphering molecular intricacies during oocyte and early embryo development as well as in addressing associated diseases. However, it is imperative to acknowledge the limitations inherent to these technologies, including the potential for off-target effects, as well as the ethical concerns surrounding the manipulation of human embryos. Thus, a judicious and thoughtful approach is warranted. Regardless of these challenges, CRISPR/Cas9 technology undeniably represents a formidable tool for genome and epigenome manipulation within oocytes and early embryos. Continuous refinements in this field are poised to fortify its future prospects and applications.
Topics: Animals; Humans; CRISPR-Cas Systems; Gene Editing; Oocytes; Embryo, Mammalian; Embryonic Development; Mammals
PubMed: 37875936
DOI: 10.1186/s12967-023-04610-9 -
Reproductive Biomedicine Online Dec 2023The objective of this review is to provide an update on planned oocyte cryopreservation. This fertility preservation method increases reproductive autonomy by allowing... (Review)
Review
The objective of this review is to provide an update on planned oocyte cryopreservation. This fertility preservation method increases reproductive autonomy by allowing women to postpone childbearing whilst maintaining the option of having a biological child. Oocyte cryopreservation is no longer considered experimental, and its use has increased dramatically in recent years as more women delay childbearing for personal, professional and financial reasons. Despite increased usage, most patients who have undergone oocyte cryopreservation have not yet warmed their oocytes. Most women who cryopreserve oocytes wait years to use them, and many never use them. Studies have demonstrated that oocyte cryopreservation results in live birth rates comparable with IVF treatment using fresh oocytes, and does not pose additional safety risks to offspring. Based on current evidence, cryopreserving ≥20 mature oocytes at <38 years of age provides a 70% chance of one live birth. However, larger studies from a variety of geographic locations and centre types are needed to confirm these findings. Additional research is also needed to determine the recommended age for oocyte cryopreservation, recommended number of oocytes to cryopreserve, return and discard/non-use rates, cost-effectiveness, and how best to distribute accurate and up-to-date information to potential patients.
Topics: Female; Humans; Pregnancy; Birth Rate; Cryopreservation; Fertility Preservation; Live Birth; Oocytes; Infant, Newborn
PubMed: 37804606
DOI: 10.1016/j.rbmo.2023.103367 -
Current Opinion in Genetics &... Aug 2023The totipotent embryo initiates transcription during zygotic or embryonic genome activation (EGA, ZGA). ZGA occurs at the 8-cell stage in humans and its failure leads to... (Review)
Review
The totipotent embryo initiates transcription during zygotic or embryonic genome activation (EGA, ZGA). ZGA occurs at the 8-cell stage in humans and its failure leads to developmental arrest. Understanding the molecular pathways underlying ZGA and totipotency is essential to comprehend human development. Recently, human 8-cell-like cells (8CLCs) have been discovered in vitro that resemble the 8-cell embryo. 8CLCs exist among naive pluripotent stem cells and can be induced genetically or chemically. Their ZGA-like transcriptome, transposable element activation, 8-cell embryo-specific protein expression, and developmental properties make them an exceptional model system to study early embryonic cell-state transitions and human totipotency programs in vitro.
Topics: Humans; Pluripotent Stem Cells; Human Embryonic Stem Cells; Zygote; Genome, Human
PubMed: 37356343
DOI: 10.1016/j.gde.2023.102066 -
Nature Communications Jul 2023Inwardly rectifying potassium (Kir) channels open at the 'helix bundle crossing' (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore....
Inwardly rectifying potassium (Kir) channels open at the 'helix bundle crossing' (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity. Single-channel recordings reveal striking, pH-dependent, subconductance behaviors in G178D (or G178E and equivalent Kir2.1[G177E]) mutant channels, with well-resolved non-cooperative subconductance levels. Decreasing cytoplasmic pH shifts the probability towards lower conductance levels. Molecular dynamics simulations show how protonation of Kir2.2[G178D], or the D173 pore-lining residues, changes solvation, K ion occupancy, and K conductance. Ion channel gating and conductance are classically understood as separate processes. The present data reveal how individual protonation events change the electrostatic microenvironment of the pore, resulting in step-wise alterations of ion pooling, and hence conductance, that appear as 'gated' substates.
Topics: Ions; Molecular Dynamics Simulation; Cytoplasm; Oocytes
PubMed: 37507406
DOI: 10.1038/s41467-023-40058-7 -
Nature Communications Nov 2023Embryo development depends upon maternally derived materials. Mammalian oocytes undergo extreme asymmetric cytokinesis events, producing one large egg and two small...
Embryo development depends upon maternally derived materials. Mammalian oocytes undergo extreme asymmetric cytokinesis events, producing one large egg and two small polar bodies. During cytokinesis in somatic cells, the midbody and subsequent assembly of the midbody remnant, a signaling organelle containing RNAs, transcription factors and translation machinery, is thought to influence cellular function or fate. The role of the midbody and midbody remnant in gametes, in particular, oocytes, remains unclear. Here, we examined the formation and function of meiotic midbodies (mMB) and mMB remnants using mouse oocytes and demonstrate that mMBs have a specialized cap structure that is orientated toward polar bodies. We show that that mMBs are translationally active, and that mMB caps are required to retain nascent proteins in eggs. We propose that this specialized mMB cap maintains genetic factors in eggs allowing for full developmental competency.
Topics: Animals; Mice; Meiosis; Oocytes; Cytokinesis; Polar Bodies; Embryonic Development; Mammals
PubMed: 37973997
DOI: 10.1038/s41467-023-43288-x